The University of Kentucky is unique among land grant universities in that all colleges, including Medicine and Agriculture, are located on the same campus. This constellation of programs has enabled the UK-SBRP to develop uniquely productive collaborations across diverse disciplines. Such an environment will allow to study the overall theme of the SBRP research, which focuses on the toxicology of Superfund chemicals and how health effects of exposure can be modulated by both intrinsic and extrinsic factors, namely genetics and nutrition, respectively. Given the abundance of Superfund chemicals and widespread distribution in the ecosystem, it is unlikely that remediation alone will be sufficient to address their health risks. Nutritional intervention thus becomes a sensible way to address health problems associated with environmental pollutants. In the competing renewal, the investigators recognize this dual need for sensing/remediation and biomedical intervention through nutrition by proposing five integrated projects. The investigators will concentrate on chlorinated organics (e.g., polychlorinated biphenyls) prevalent in most Superfund sites, including those found in Kentucky. Preliminary findings by this group suggest that nutrition and dietary habits can markedly influence mechanisms of toxicity of the above-mentioned Superfund chemicals. Thus, a major objective of our SBRP is to explore the paradigm that nutrition can modify Superfund chemical toxicity. All biomedical projects will focus on chronic diseases associated with vascular dysfunction, such as cardiovascular disease, cancer metastasis, and obesity-related abdominal aortic aneurysms, and will utilize a similar dietary fat regimen to study nutrient/toxicant interactions. There will be significant cross-talk with non-biomedical projects, which will explore novel techniques for both remediation (detoxification) and biosensors associated with detection of PCBs and other chlorinated organics. Results from interdisciplinary research will be utilized for information/education, technology transfer, training, policy and translational purposes as part of the objectives of the Research Translation, Community Outreach, and Training Cores. Nutrition may be the most sensible means to develop primary prevention strategies of diseases associated with many environmental toxic insults. Thus, research proposed by the investigators may lead to novel dietary recommendations at the national level for populations at risk, thus improving the health of people residing near Superfund sites. ADMINISTRATIVE CORE Description (provided by applicant) The Administrative Core (Core A) will oversee the entire Superfund Basic Research Program through a management mechanism that allows efficient and accountable oversight and maximum interdisciplinary and multidisciplinary interactions among all participants. The Administrative Core will be responsible for the coordination, planning, assessment, project accounting, and administrative support to the research personnel of the University of Kentucky SBRP. A major objective of the Administrative Core is to facilitate the execution of an interdisciplinary research theme through administrative support and fiscal accountability. The Administrative Core will work especially closely with the Research Translation Core (Core C) to optimize communication with NIEHS, EPA, and state and local constituents;communication is also facilitated by an active website that is managed by Core C with input from the Administrative Core. Research efforts will be coordinated through biweekly meetings of faculty, students and research staff, as well as seminars, where new findings and planned activities and ideas will be discussed. It will also be critical to discuss research findings for informative/educational activities, technology transfer, training, policy and translational purposes as part of the objectives of the Research Translation, Community Outreach, and Training Cores. The Administrative Core will implement feedback and cross-talk between all project and core activities to allow for maximum integration. For example, optimal detection and remediation of Superfund pollutants must be linked to risk assessment and biomedical aspects of degradation products. Accountability of the University of Kentucky SBRP activities, including the quality of science and administration, will be achieved through regular consultations with both the External and Internal Advisory Boards. Research quality assessment and statistical consultation will be managed through the Research Support Core. General fiscal responsibilities or project accounting will be coordinated through the Administrative Office in conjunction with the University of Kentucky Research Foundation. The Program Coordinator together with the Program Director will serve as a regular contact among all SBRP activities, including research projects and cores, and will coordinate all reports required by the sponsoring agencies.